Pathogenesis of bronchopulmonary dysplasia in preterm neonates revealed by an RNA sequencing interaction network analysis.

ABSTRACT

Background: The chronic lung condition known as bronchopulmonary dysplasia (BPD), which primarily affects newborns, especially preterm neonates, is brought on by prolonged oxygen consumption and mechanical ventilation. This case-control study sought to investigate the pathogenesis of BPD in preterm neonates by RNA sequencing (RNA-seq). Methods: First, RNA-seq samples were collected from 3 BPD and 3 healthy preterm neonates. Based on the sequencing data and microarray data sets, MERGE.57185.1, the key long non-coding RNA (lncRNA), was identified from the differentially expressed lncRNAs and the key module by a weighted gene co-expression network analysis (WGCNA), a Venn diagram, and an expression analysis. Next, the differentially expressed messenger RNAs (mRNAs) and microRNAs (miRNAs) that were strongly correlated to MERGE.57185.1 were identified in the protein-protein interaction networks and underwent a functional enrichment analysis and Spearman correlation analysis. Finally, the mRNA [i.e., eukaryotic translation initiation factor 5A (EIF5A)] and miRNA (i.e., hsa-miR-6833-5p) with the strongest correlations to MERGE.57185.1 were identified as the downstream targets. Results: Among the 32 genes in the dark-red module and the 158 differentially expressed lncRNAs, 21 overlapping genes were identified. In the gene expression analysis, MERGE.57185.1 (an oncogene) was identified as the key lncRNA in BPD. The results of the multiple bioinformatics analysis showed that the mRNA and the miRNA with the strongest correlations to MERGE.57185.1 were hsa-miR-6833-5p (a suppressor gene) and EIF5A (an oncogene), respectively. Hsa-miR-6833-5p was lowly expressed in the BPD group, while EIF5A was highly expressed in the BPD group. Conclusions: This study identified 1 key upregulated lncRNA (i.e., MERGE.57185.1) in preterm neonatal BPD, and revealed the MERGE.57185.1/hsa-miR-6833-5p/EIF5A mechanism in preterm neonatal BPD from the lncRNA-miRNA-mRNA network. This key lncRNA gene could serve as a promising diagnostic biomarker for prenatal examinations.